• Mitotic checkpoint serine/threonine-protein kinase BUB1 is a protein in humans that is encoded by BUB1 gene. (cusabio.com)
  • Serine/threonine-protein kinase that performs 2 crucial functions during mitosis. (cusabio.com)
  • These paclitaxel resistant ovarian cells demonstrate: (1) Increased IC 50 for paclitaxel and docetaxel (10 to 75-fold) and cross-resistance to anthracyclines (2) Reduced cell apoptosis in the presence of paclitaxel (3) Gene depletion involving mitotic regulators BUB1 mitotic checkpoint serine/threonine kinase, cyclin BI (CCNB1), centromere protein E (CENPE), and centromere protein F (CENPF), and (4) Functional data validating gene depletion among mitotic regulators. (biomedcentral.com)
  • Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. (icr.ac.uk)
  • NEK2 is a member of the NIMA-related family of serine/threonine centrosomal kinases. (oncotarget.com)
  • 2016. In silico analysis of deleterious single nucleotide polymorphisms in human BUB1 mitotic checkpoint serine/threonine kinase B gene. (ac.ir)
  • Development through mitosis depends upon three major regulatory systems, each involving several serine/threonine kinases, referred to as mitotic kinases. (survivinpathway.com)
  • Rabbit anti ATM antibody recognizes serine-protein kinase ATM, also known as ataxia telangiectasia mutated. (bio-rad-antibodies.com)
  • ATM is a serine/threonine protein kinase and a member of the PI3K/P14K-kinase family. (bio-rad-antibodies.com)
  • Decreased expression of six RNA species was seen at various time points in all cell strains analyzed, these were: plasminogen activator (PLAT), centromere protein F (CPF), replication factor C (RFC3), thymidylate synthetase (TYMS), a putative mitotic checkpoint kinase (BUB1) and a gene of unknown function (GenBank accession number AI859865). (cdc.gov)
  • The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. (icr.ac.uk)
  • Luckily, eukaryotic cells not only possess an error-correction machinery deputed to rectify faulty attachments ( 2 ), but they also have a safeguard device, called the spindle assembly checkpoint (SAC), that temporarily halts cells in mitosis to provide them with the necessary time window to fix the errors. (rupress.org)
  • BAL0891 is a first-in-class mitotic checkpoint inhibitor that pushes cells through mitosis without adequate time for correct chromosome segregation. (basilea.com)
  • NEK6 belongs to the never in mitosis A (NIMA)-related kinases family and is a mitogen/threonine kinase with 313 amino acids. (hindawi.com)
  • Within this review, we summarize the functions that all of the Aurora kinases has in cancer biology and mitosis, and discuss the binding modes of Aurora A kinase inhibitors, the spot elements in the binding sites and the fortunate inhibitor components. (survivinpathway.com)
  • At the onset of mitosis, centrosomes become the core structures of spindle poles and direct the formation of mitotic spindles. (biomedcentral.com)
  • In early mitosis, the cohesion between the two pairs of centrioles is broken and each of them participates in the formation of the mitotic spindle pole. (biomedcentral.com)
  • During mitosis the two centrosomes are present and form the mitotic spindle poles. (biomedcentral.com)
  • kinase in candida, is an important mitosis regulatory proteins encoded on human being chromosome 20q13.2 that induces oncogenic change followed with centrosome amplification and aneuploidy when over indicated SEMA3E in rodent cells and (6-8). (arcillaresearch.com)
  • Inhibition of DNA-PKcs activity via a small interfering RNA or a kinase inhibitor results in mitosis delay, abnormal spindle formation, and chromosome misalignment. (amegroups.org)
  • Prevailing models posit that a key trigger of SAC signaling is the phosphorylation of the kinetochore scaffold KNL1 by the SAC kinase MPS1. (rupress.org)
  • MPS1 belongs to a family of proteins called mitotic checkpoint kinases, responsible for correctly organising cell division. (cancerresearchuk.org)
  • The mitotic checkpoint gene MPS1 was themost significant gene correlated with TP53 status, and the most significant prognostic markerin all ER-positive BC datasets. (mtak.hu)
  • The mitotic kinase monopolar spindle 1 (Mps1) is a key regulator of the Spindle assembly checkpoint, which ensures the correct chromosome segregation. (lu.se)
  • We could confirm the increased polyploidy upon Mps1 inhibition in neuroblastoma cell lines and PDX model, leading to mitotic catastrophe activating the caspase-dependent mitochondrial apoptotic pathway. (lu.se)
  • After PLK1 inhibition, ARAC-02 transiently upregulates PD-L1 expression, rendering the cancer (which may originally have low PD-L1 expression and are not eligible for immune checkpoint inhibitors, ICIs) more sensitive to PD-L1 antibody serving as the ICI and cancer homing agent on ARAC-02. (ohsu.edu)
  • BAL0891 is differentiated through its unique kinase inhibition profile targeting both threonine tyrosine kinase and polo-like kinase 1. (basilea.com)
  • Combined Aurora kinase and EGFR targeting using a monoclonal anti-EGFR antibody was more effective compared to single EGFR and Aurora kinase inhibition. (oncotarget.com)
  • Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. (icr.ac.uk)
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key component of the non-homologous end-joining (NHEJ) pathway, is involved in DNA double-strand break repair, immunocompetence, genomic integrity, and epidermal growth factor receptor signaling. (amegroups.org)
  • The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is the key component of the non-homologous end-joining (NHEJ) pathway for DNA double-strand break (DSB) repair and is required for cellular resistance to ionizing radiation (IR) ( 1 , 2 ). (amegroups.org)
  • NTRC is a privately owned biotech company based in Oss in the Netherlands that has two subsidiary companies: NTRC Therapeutics B.V. and Oncolines B.V. NTRC Therapeutics is a precision medicine company that is specialized in discovery and development of innovative kinase inhibitors to treat cancer patients. (basilea.com)
  • Using its proprietary EPriL platform NTRC Therapeutics is now developing next-generation kinase inhibitors to treat acquired drug resistance observed in cancer patients treated with first generation inhibitors. (basilea.com)
  • Our report on the reported chemical scaffolds of Aurora A kinase inhibitors and their binding modes could give a of good use Letrozole ic50 framework from which new design strategies for inhibitors may be evaluated or produced. (survivinpathway.com)
  • In addition, we review the main pre-clinical and clinical studies concerning Aurora kinase inhibitors currently under investigation. (survivinpathway.com)
  • The extensive pre-clinical data supports the develop-ment of focused Aurora kinase inhibitors in certain tumefaction types. (survivinpathway.com)
  • It also directly binds to BubR1, a kinetochore-associated kinase implicated in the mitotic checkpoint, the major cell cycle control pathway in which unattached kinetochores prevent anaphase onset. (rupress.org)
  • Without CENP-E, diminished levels of BubR1 are recruited to kinetochores and BubR1 kinase activity remains at basal levels. (rupress.org)
  • CENP-E binds to and directly stimulates the kinase activity of purified BubR1 in vitro. (rupress.org)
  • Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal. (rupress.org)
  • Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. (icr.ac.uk)
  • The activity of NEK6 plays important roles in mitotic spindle kinetochore fiber formation, metaphase-anaphase transition, cytokinesis, and checkpoint regulation [ 3 , 4 ]. (hindawi.com)
  • Fig. 1 ), which in turn attracts to the kinetochore other SAC proteins that collectively prevent mitotic progression ( 3 ). (rupress.org)
  • Any process that stops, prevents, or reduces the frequency, rate or extent of the movement of proteins from the cytoplasm into the nucleus, and that occurs as a response to the mitotic cell cycle spindle assembly checkpoint. (yeastgenome.org)
  • Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.com)
  • The compound is a unique dual inhibitor of threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1). (basilea.com)
  • Treating SCCHN cell lines with a pan-Aurora kinase inhibitor resulted in defective cytokinesis, polyploidy and apoptosis, which was effective irrespective of the EGFR status. (oncotarget.com)
  • It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death. (tocris.com)
  • Furthermore, DNA-PKcs is required to prevent mitotic catastrophe in response to DNA damage ( 13 ). (amegroups.org)
  • Glc7p functions in opposition to key spindle assembly checkpoint protein Aurora kinase (Ipl1p). (yeastgenome.org)
  • We analyzed the clinical data and performed immunohistochemistry for Epidermal growth factor receptor (EGFR) and Aurora kinase A (Aurora-A) expression in 180 SCCHN patients. (oncotarget.com)
  • Comparing pan-Aurora kinase and Aurora-A targeting hints towards a strong and clinically relevant biological effect mediated via Aurora kinase B. Taken together, our findings characterize a new poor risk group in SCCHN patients defined by elevated EGFR and Aurora-A protein expression. (oncotarget.com)
  • Our results demonstrate that combined targeting of EGFR and Aurora kinases represents a therapeutic means to activate cell cycle checkpoints and apoptosis in SCCHN. (oncotarget.com)
  • The Aurora kinases really are a group of three highly homologous Ser/ Thr protein kinases, including Aurora A, B and C. (survivinpathway.com)
  • Background Aurora kinase A (AURKA) is amplified with varying occurrence in multiple human being cancers including mind and throat squamous cell carcinoma (HNSCC). (arcillaresearch.com)
  • Aurora Kinase-A gene is usually amplified and overexpressed in lots of human malignancies, including colorectal, breasts, ovarian, bladder, gastric and pancreatic malignancies. (arcillaresearch.com)
  • Centromere-associated protein-E (CENP-E) is an essential mitotic kinesin that is required for efficient, stable microtubule capture at kinetochores. (rupress.org)
  • PIG3 knockdown led to an abnormal DNA damage response, including decreased IR-induced phosphorylation of H2AX, Chk1, Chk2 and Kap-1 as well as a prolonged G2-M arrest and aberrant mitotic progression. (ijbs.com)
  • This phosphorylation is regulated by the ataxia telangiectasia mutated (ATM) and the Rad3-related (ATR) kinases in response to various genotoxic stresses, making it a critical regulatory element of DNA-PKcs ( 6 , 10 ). (amegroups.org)
  • DNA-PKcs activation, as monitored by DNA-PKcs phosphorylation, is physically and functionally associated with mitotic spindle formation. (amegroups.org)
  • Checkpoint control kinases is a term used to describe a group of enzymes that regulate progression of a cell through the cell cycle. (tocris.com)
  • A better understanding of the CDK2 substrates will help us to gain deeper insight into the functions of this universal kinase. (lu.se)
  • PC/DX25 with greater resistance to docetaxel had higher levels of acetyl-tubulin and mitotic centromere-associated kinesin (MCAK) than PC3 cells. (bvsalud.org)
  • Overexpression of polo-like kinase-1 increased the cell survival rate and resistance to docetaxel in PC3 cells. (bvsalud.org)
  • 6, 9-13) Furthermore, AURKA overexpression overrides the mitotic spindle checkpoint and promotes level of resistance to paclitaxel Taxol. (arcillaresearch.com)
  • We have generated model systems to explore drug resistance in ovarian cancer, which have revealed a key pathway related to the spindle assembly checkpoint underlying paclitaxel resistance in ovarian cell lines. (biomedcentral.com)
  • Lastly, through gene expression profiling we have demonstrated disruption of the spindle assembly checkpoint in the paclitaxel resistant cell lines, indicating a potential therapeutic pathway. (biomedcentral.com)
  • Previous evidence points to numerous components of the spindle assembly checkpoint and mitotic regulation playing a major role in several cancers [ 11 , 12 ]. (biomedcentral.com)
  • For a cell to progress through the cycle and replicate, it must pass through checkpoints between phases to ensure that DNA is replicated correctly and that chromosomes segregate. (tocris.com)
  • Basilea Pharmaceutica Ltd. (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with cancer and infectious diseases, announced today that the U.S. Food and Drug Administration (FDA) has approved the company's Investigational New Drug (IND) application for the novel kinase inhibitor BAL0891, a potential first-in-class mitotic checkpoint inhibitor (MCI) that drives aberrant tumor cell division leading to tumor cell death. (basilea.com)
  • Silencing of the spindle assembly checkpoint involves two protein phosphatases, PP1 and PP2A-B56, that are thought to extinguish checkpoint signaling through dephosphorylation of a checkpoint scaffold at kinetochores. (rupress.org)
  • Both kinases collaborate in activating the mitotic spindle assembly checkpoint (SAC), a cell division mechanism regulating correct chromosome alignment and segregation. (basilea.com)
  • ARAC-02 - nanoparticle co-delivering a PD-L1 antibody, a polo-like kinase 1 (PLK1) inhibitor, and an immune-stimulant CpG - provides effective antitumor immune response via CD8+ T cell activities. (ohsu.edu)
  • Silencing the spindle assembly checkpoint: Let's play Polo! (rupress.org)
  • PIG3 knockdown can suppress intra-S phase and G2/M checkpoints ( 8 ). (ijbs.com)
  • The Yantasee lab at OHSU in collaboration with PDX Pharmaceuticals has been awarded a phase II SBIR grant of $1.87M for 2 years from the National Cancer Institute (NCI) focusing on the development of a new nano-immunotherapy ARAC-02 (Antigen Release Agent and Checkpoint Inhibitor) for lung cancer treatment. (ohsu.edu)
  • Here we identify CSNK1E , the gene encoding casein kinase 1 epsilon (CK1ε) as required specifically for the proliferation of breast cancer cells with activated β-catenin and confirm its role as a positive regulator of β-catenin-driven transcription. (plos.org)
  • Impaired spindle checkpoint function has been found in many forms of cancer. (utsouthwestern.edu)
  • Targeting the cell cycle has been proposed as a therapeutic strategy in cancer treatment with special interest in the mitotic phase. (lu.se)
  • Treatment with the novel cyclophilin inhibitor NV651, presented a potent antiproliferative effect in HCC cell lines via cell cycle perturbations arresting cells in the mitotic phase. (lu.se)
  • Checkpoint control kinases function to halt the cell cycle at these critical points. (tocris.com)
  • Tocris offers the following scientific literature for Checkpoint Control Kinases to showcase our products. (tocris.com)
  • https://doi.org/10.1083/jcb.202002020 ) now show that a critical function of these phosphatases in checkpoint silencing is removal of Polo kinase at kinetochores, which would otherwise autonomously sustain the checkpoint. (rupress.org)
  • This gene encodes a kinase involved in spindle checkpoint function. (utsouthwestern.edu)
  • J-H Lee et al extensively investigated the participation of PIG3 in DNA damage checkpoints after UV irradiation or after treatment using the radiomimetic drug neocarzinostatin (NCS) ( 8 ). (ijbs.com)
  • We are looking forward to adding this potential first-in-class mitotic checkpoint inhibitor to our clinical oncology pipeline. (basilea.com)